1. Field of the Invention
The present invention relates to sugar transferases and the genes encoding said enzymes. More specifically, the present invention relates to ceramide glucosyltransferases, i.e., glucosylceramide synthetases catalyzing glucose transfer, and to genes encoding the enzymes.
2. Description of Related Art
Glycosphingolipids (GSLs) are a class of membrane components that have the lipid portion embedded in the outer leaflet of the lipid bilayer of plasma membrane and the sugar chains extended to the outer environment. Glycosphingolipids exist essentially in all of the animal cells and are suggested as being important substances responsible for various cellular processes such as differentiation, adhesion, proliferation, and cell--cell recognition (Varki, A., Glycobiology, 3, pp.97-130, 1993).
With only a few exceptions, almost all of the glycolipids are synthesized from glucosylceramide as a precursor that is produced by the transfer of glucose to ceramide. Ceramide glucosyltransferase (UDP-glucose: ceramide .beta. 1-1' glucosyltransferase, GlcT-1, EC2.4.1.80: hereinafter in the specification, this enzyme is occasionally referred to simply as "ceramide glucosyltransferase.") catalyzes the first glycosylation step of the glycosphingolipid biosyntheses, i.e., the transfer of glucose from UDP-Glc to ceramide (Basu, S. et al., J. Biol. Chem., 243, pp.5802-5807, 1968). Glucosylceramide (GlcCer), the product of this enzyme, serves as precursors for more than 300 of glycosphingolipid biosyntheses (Radin, N. S., Nuerochem. Res., 5, pp.533-540, 1994).
GlcT-1 was first discovered from embryonic chick brain (Basu, S. et al., J. Biol. Chem., 243, pp.5802-5807, 1968). However, the properties of the enzyme have not been fully studied, because of the difficulties in assaying and purifying the enzyme. Only limited data have been published concerning GlcT-1 so far, e.g. successful solubilization of the enzyme from rat Golgi fraction (Durieux, I. et al., Biochem. Biophys. Acta, 1024, pp.263-266, 1990) and discovery of the enzymes in liver and brain each characterized by distinguishable properties (Vunnam, R. et al., Biochem. Biophys.
Acta, 573, pp.73-82, 1979). It has recently been revealed that the synthesis of GlcCer occurs at the cytosolic surface of Golgi apparatus, while other glycosylation reactions in biosynthetic pathways of glycosphingolipid take place at the lumenal side of the organelle. However, the most of enzymatic properties of the ceramide glucosyltransferases remain unknown. As for ceramide galactosyltransferase, having a similar catalytic activity, the cloning of the enzyme was reported (Schulte, S. et al., Proc. Natl. Acad. Sci. USA, 90, pp.10265-10269, 1993).